Mammalian cell cultures are very useful for the production of certain products, such as viral vaccines, interferons, recombinant therapeutic proteins, and monoclonal antibodies. However, these cell cultures also carry inherent limitations, such as a very slow growth rate, low biomass density, the requirement for a complex media, and high operational costs.
Microbial expression systems have numerous advantages for the production of useful proteins. While certain microbial systems are useful for producing, simple proteins, such microbial systems would need to be improved in terms of the quality and complexity of proteins that can be produced. The improvement of microbial cell specific productivities requires complex engineering, and substantial understanding and rewiring of the underlying microbial metabolism. An ideal strain would be genetically stable, have a high specific and volumetric productivity, form no by-products, and use a well-defined medium. These characteristics would allow for downstream processing with a limited number of steps.
Labyrinthulomycetes are robustly fermentable eukaryotic microalgae. These heterotrophic microorganisms are recognized for their industrial ability to consume sugar and store large amounts of cellular oils as triglycerides; the most commercially important is docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA) that is a major component of fish oil. These organisms produce oils that can be used in human and animal nutritional supplements, as well as for food fortification applications. These triglyceride oils can be produced in culture using inexpensive media. Because of these desirable qualities it would be advantageous to have recombinant Labyrinthulomycetes cells that are able to produce a variety of proteins or therapeutic proteins, including functional antibodies that can have both heavy and light chains.